Translational Immunology Core

Project Summary/Abstract – Translational Immunology Core There are several virus families with serious pandemic potential but for which we currently have no effective vaccines. Development of new vaccines (and new vaccine technologies) against these infectious diseases will be critical for protecting Americans, and the world, from future pandemics. A major challenge in vaccine

development is assessing the translational potential of a candidate from small animal models to larger animal models and humans. Unfortunately, most vaccines that show protection in mice do not result in protection when tested in human clinical trials. To help de-risk these translational steps and establish mechanisms of protection

across multiple animal and in vitro models, the translational immunology core will collect comprehensive immunogenicity and safety data in non-human primates (NHP) and test vaccine candidates for the ability to stimulate human adaptive immune responses in an organoid model. We hypothesize that establishing correlates

of protection and detailed mechanistic data from multiple sources (murine immunogenicity and challenge data, non-human primate immunogenicity and challenge data, and human immune organoids) will accelerate the identification of common features that promote protective immunity in humans. The goal of the Translational

Immunology Core will be to support each of the individual projects by testing the most promising vaccine candidates in non-human primates (Aim 1) and a human immune organoid model (Aim 2). We will conduct deep serum antibody profiling from both NHP and human cohorts (Aim 3). We will collect comprehensive

immunogenicity and reactogenicity data in a rhesus macaque cohort, including dosing, overall animal health, and innate and adaptive immune measurements. Lymphoid tissues from immunized animals will also be used for in vitro immune organoid testing. In Aim 2, NHP and human lymphoid tissues will be stimulated (or

restimulated) with vaccine candidates in vitro and numerous metrics of productive adaptive immune responses, including B and T cell activation, germinal center activity, and antibody magnitude, breadth, avidity, and function will be established. The novelty of this core lies in our systems immunology approach to integrate health,

serological, phenotypic, functional, and repertoire readouts in well-controlled platforms. Completion of the proposed experiments will help us rapidly identify correlates of protection and guide the design and refinements of novel vaccines against Bunyaviruses, Paramyxoviruses, and Picornaviruses and directly contribute to and

support the individual projects in this proposal.